Loading…
Enantiomer-Specific In Vitro Biotransformation of Select Pharmaceuticals in Rainbow Trout (Oncorhynchus mykiss)
ABSTRACT The occurrence of pharmaceuticals in the environment represents a challenge of emerging concern. Many pharmaceuticals are chiral compounds; however, few studies have examined the relative toxicity of pharmaceutical enantiomers to wildlife. Further, our understanding of stereospecific pharma...
Saved in:
Published in: | Chirality (New York, N.Y.) N.Y.), 2013-11, Vol.25 (11), p.763-767 |
---|---|
Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c4611-a75734d094897d7c16cd3753960628a4e58ede82063b4bffea80b5a0b57df8433 |
---|---|
cites | cdi_FETCH-LOGICAL-c4611-a75734d094897d7c16cd3753960628a4e58ede82063b4bffea80b5a0b57df8433 |
container_end_page | 767 |
container_issue | 11 |
container_start_page | 763 |
container_title | Chirality (New York, N.Y.) |
container_volume | 25 |
creator | Connors, Kristin A. Du, Bowen Fitzsimmons, Patrick N. Chambliss, C. Kevin Nichols, John W. Brooks, Bryan W. |
description | ABSTRACT
The occurrence of pharmaceuticals in the environment represents a challenge of emerging concern. Many pharmaceuticals are chiral compounds; however, few studies have examined the relative toxicity of pharmaceutical enantiomers to wildlife. Further, our understanding of stereospecific pharmacokinetics remains largely informed by research on humans and a few well‐studied laboratory test animals, and not by studies conducted with environmentally relevant species, including fish. The objective of this study was to investigate whether rainbow trout display stereospecific in vitro metabolism of three common chiral pharmaceuticals. Metabolism by trout liver S9 fractions was evaluated using a substrate depletion approach, which provides an estimate of intrinsic hepatic clearance (CLIN VITRO,INT). No biotransformation was observed for rac‐, R‐, or S‐fluoxetine. Ibuprofen, including both enantiomers and the racemic mixture, appeared to undergo slow metabolism, but the resulting substrate depletion curves did not differ significantly from those of inactive controls. Contrary to relative clearance rates in humans, S(−)‐propranolol was more rapidly cleared than the R(+)‐ enantiomer. This work demonstrates that relative clearance rates and the effects of racemic mixtures in trout could not have been predicted based on human data. Additional research describing species differences and exploring tools for species extrapolation in biomedical and environmental studies is needed. Chirality 25:763–767, 2013, © 2013 Wiley Periodicals, Inc. |
doi_str_mv | 10.1002/chir.22211 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1758239307</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3107302441</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4611-a75734d094897d7c16cd3753960628a4e58ede82063b4bffea80b5a0b57df8433</originalsourceid><addsrcrecordid>eNqN0U1rFDEYB_Agil2rFz-ABLxUYWreX47t0m4XipW2Wm8hk8mwaWeSNZmh7rfvrNv24EE8hED4PX_I8wfgPUaHGCHyxa1CPiSEYPwCzDAnqBJU_HwJZkhpXSHEyB54U8otQkgLyl6DPUKVplKSGUgn0cYhpN7n6mrtXWiDg8sIf4QhJ3gc0pBtLG3KvZ1UhKmFV77zboDfVnZ6dH4cgrNdgSHCSxtine7hdU7jAA8uokt5tYluNRbYb-5CKZ_eglftpP27x3sffD89uZ6fVecXi-X86LxyTGBcWcklZQ3STGnZSIeFa6jkVAskiLLMc-UbrwgStGZ123qrUM3tdGTTKkbpPjjY5a5z-jX6Mpg-FOe7zkafxmKw5IpQTZH8D8qY0JppPNGPf9HbNOY4fcRgxhhnXPBt4OedcjmVkn1r1jn0Nm8MRmbbmNk2Zv40NuEPj5Fj3fvmmT5VNAG8A_eh85t_RJn52fLyKbTazYQy-N_PMzbfGSGnPZqbrwsj5vJY3hBlFvQBAy2vMA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1444545657</pqid></control><display><type>article</type><title>Enantiomer-Specific In Vitro Biotransformation of Select Pharmaceuticals in Rainbow Trout (Oncorhynchus mykiss)</title><source>Wiley</source><creator>Connors, Kristin A. ; Du, Bowen ; Fitzsimmons, Patrick N. ; Chambliss, C. Kevin ; Nichols, John W. ; Brooks, Bryan W.</creator><creatorcontrib>Connors, Kristin A. ; Du, Bowen ; Fitzsimmons, Patrick N. ; Chambliss, C. Kevin ; Nichols, John W. ; Brooks, Bryan W.</creatorcontrib><description>ABSTRACT
The occurrence of pharmaceuticals in the environment represents a challenge of emerging concern. Many pharmaceuticals are chiral compounds; however, few studies have examined the relative toxicity of pharmaceutical enantiomers to wildlife. Further, our understanding of stereospecific pharmacokinetics remains largely informed by research on humans and a few well‐studied laboratory test animals, and not by studies conducted with environmentally relevant species, including fish. The objective of this study was to investigate whether rainbow trout display stereospecific in vitro metabolism of three common chiral pharmaceuticals. Metabolism by trout liver S9 fractions was evaluated using a substrate depletion approach, which provides an estimate of intrinsic hepatic clearance (CLIN VITRO,INT). No biotransformation was observed for rac‐, R‐, or S‐fluoxetine. Ibuprofen, including both enantiomers and the racemic mixture, appeared to undergo slow metabolism, but the resulting substrate depletion curves did not differ significantly from those of inactive controls. Contrary to relative clearance rates in humans, S(−)‐propranolol was more rapidly cleared than the R(+)‐ enantiomer. This work demonstrates that relative clearance rates and the effects of racemic mixtures in trout could not have been predicted based on human data. Additional research describing species differences and exploring tools for species extrapolation in biomedical and environmental studies is needed. Chirality 25:763–767, 2013, © 2013 Wiley Periodicals, Inc.</description><identifier>ISSN: 0899-0042</identifier><identifier>EISSN: 1520-636X</identifier><identifier>DOI: 10.1002/chir.22211</identifier><identifier>PMID: 23893772</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; bioaccumulation ; Biotransformation ; Clearances ; comparative pharmacokinetics ; contaminants of emerging concern ; Depletion ; Enantiomers ; Environmental Pollutants - chemistry ; Environmental Pollutants - metabolism ; environmental risk assessment ; Human ; In vitro testing ; metabolic biotransformation ; Metabolism ; Oncorhynchus mykiss ; Oncorhynchus mykiss - metabolism ; Pharmaceutical Preparations - chemistry ; Pharmaceutical Preparations - metabolism ; Pharmaceuticals ; Stereoisomerism ; Substrate Specificity ; Trout</subject><ispartof>Chirality (New York, N.Y.), 2013-11, Vol.25 (11), p.763-767</ispartof><rights>2013 Wiley Periodicals, Inc</rights><rights>2013 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4611-a75734d094897d7c16cd3753960628a4e58ede82063b4bffea80b5a0b57df8433</citedby><cites>FETCH-LOGICAL-c4611-a75734d094897d7c16cd3753960628a4e58ede82063b4bffea80b5a0b57df8433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23893772$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Connors, Kristin A.</creatorcontrib><creatorcontrib>Du, Bowen</creatorcontrib><creatorcontrib>Fitzsimmons, Patrick N.</creatorcontrib><creatorcontrib>Chambliss, C. Kevin</creatorcontrib><creatorcontrib>Nichols, John W.</creatorcontrib><creatorcontrib>Brooks, Bryan W.</creatorcontrib><title>Enantiomer-Specific In Vitro Biotransformation of Select Pharmaceuticals in Rainbow Trout (Oncorhynchus mykiss)</title><title>Chirality (New York, N.Y.)</title><addtitle>Chirality</addtitle><description>ABSTRACT
The occurrence of pharmaceuticals in the environment represents a challenge of emerging concern. Many pharmaceuticals are chiral compounds; however, few studies have examined the relative toxicity of pharmaceutical enantiomers to wildlife. Further, our understanding of stereospecific pharmacokinetics remains largely informed by research on humans and a few well‐studied laboratory test animals, and not by studies conducted with environmentally relevant species, including fish. The objective of this study was to investigate whether rainbow trout display stereospecific in vitro metabolism of three common chiral pharmaceuticals. Metabolism by trout liver S9 fractions was evaluated using a substrate depletion approach, which provides an estimate of intrinsic hepatic clearance (CLIN VITRO,INT). No biotransformation was observed for rac‐, R‐, or S‐fluoxetine. Ibuprofen, including both enantiomers and the racemic mixture, appeared to undergo slow metabolism, but the resulting substrate depletion curves did not differ significantly from those of inactive controls. Contrary to relative clearance rates in humans, S(−)‐propranolol was more rapidly cleared than the R(+)‐ enantiomer. This work demonstrates that relative clearance rates and the effects of racemic mixtures in trout could not have been predicted based on human data. Additional research describing species differences and exploring tools for species extrapolation in biomedical and environmental studies is needed. Chirality 25:763–767, 2013, © 2013 Wiley Periodicals, Inc.</description><subject>Animals</subject><subject>bioaccumulation</subject><subject>Biotransformation</subject><subject>Clearances</subject><subject>comparative pharmacokinetics</subject><subject>contaminants of emerging concern</subject><subject>Depletion</subject><subject>Enantiomers</subject><subject>Environmental Pollutants - chemistry</subject><subject>Environmental Pollutants - metabolism</subject><subject>environmental risk assessment</subject><subject>Human</subject><subject>In vitro testing</subject><subject>metabolic biotransformation</subject><subject>Metabolism</subject><subject>Oncorhynchus mykiss</subject><subject>Oncorhynchus mykiss - metabolism</subject><subject>Pharmaceutical Preparations - chemistry</subject><subject>Pharmaceutical Preparations - metabolism</subject><subject>Pharmaceuticals</subject><subject>Stereoisomerism</subject><subject>Substrate Specificity</subject><subject>Trout</subject><issn>0899-0042</issn><issn>1520-636X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqN0U1rFDEYB_Agil2rFz-ABLxUYWreX47t0m4XipW2Wm8hk8mwaWeSNZmh7rfvrNv24EE8hED4PX_I8wfgPUaHGCHyxa1CPiSEYPwCzDAnqBJU_HwJZkhpXSHEyB54U8otQkgLyl6DPUKVplKSGUgn0cYhpN7n6mrtXWiDg8sIf4QhJ3gc0pBtLG3KvZ1UhKmFV77zboDfVnZ6dH4cgrNdgSHCSxtine7hdU7jAA8uokt5tYluNRbYb-5CKZ_eglftpP27x3sffD89uZ6fVecXi-X86LxyTGBcWcklZQ3STGnZSIeFa6jkVAskiLLMc-UbrwgStGZ123qrUM3tdGTTKkbpPjjY5a5z-jX6Mpg-FOe7zkafxmKw5IpQTZH8D8qY0JppPNGPf9HbNOY4fcRgxhhnXPBt4OedcjmVkn1r1jn0Nm8MRmbbmNk2Zv40NuEPj5Fj3fvmmT5VNAG8A_eh85t_RJn52fLyKbTazYQy-N_PMzbfGSGnPZqbrwsj5vJY3hBlFvQBAy2vMA</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Connors, Kristin A.</creator><creator>Du, Bowen</creator><creator>Fitzsimmons, Patrick N.</creator><creator>Chambliss, C. Kevin</creator><creator>Nichols, John W.</creator><creator>Brooks, Bryan W.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QR</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>JG9</scope><scope>L7M</scope><scope>F1W</scope><scope>H95</scope><scope>L.G</scope></search><sort><creationdate>201311</creationdate><title>Enantiomer-Specific In Vitro Biotransformation of Select Pharmaceuticals in Rainbow Trout (Oncorhynchus mykiss)</title><author>Connors, Kristin A. ; Du, Bowen ; Fitzsimmons, Patrick N. ; Chambliss, C. Kevin ; Nichols, John W. ; Brooks, Bryan W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4611-a75734d094897d7c16cd3753960628a4e58ede82063b4bffea80b5a0b57df8433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>bioaccumulation</topic><topic>Biotransformation</topic><topic>Clearances</topic><topic>comparative pharmacokinetics</topic><topic>contaminants of emerging concern</topic><topic>Depletion</topic><topic>Enantiomers</topic><topic>Environmental Pollutants - chemistry</topic><topic>Environmental Pollutants - metabolism</topic><topic>environmental risk assessment</topic><topic>Human</topic><topic>In vitro testing</topic><topic>metabolic biotransformation</topic><topic>Metabolism</topic><topic>Oncorhynchus mykiss</topic><topic>Oncorhynchus mykiss - metabolism</topic><topic>Pharmaceutical Preparations - chemistry</topic><topic>Pharmaceutical Preparations - metabolism</topic><topic>Pharmaceuticals</topic><topic>Stereoisomerism</topic><topic>Substrate Specificity</topic><topic>Trout</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Connors, Kristin A.</creatorcontrib><creatorcontrib>Du, Bowen</creatorcontrib><creatorcontrib>Fitzsimmons, Patrick N.</creatorcontrib><creatorcontrib>Chambliss, C. Kevin</creatorcontrib><creatorcontrib>Nichols, John W.</creatorcontrib><creatorcontrib>Brooks, Bryan W.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><jtitle>Chirality (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Connors, Kristin A.</au><au>Du, Bowen</au><au>Fitzsimmons, Patrick N.</au><au>Chambliss, C. Kevin</au><au>Nichols, John W.</au><au>Brooks, Bryan W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enantiomer-Specific In Vitro Biotransformation of Select Pharmaceuticals in Rainbow Trout (Oncorhynchus mykiss)</atitle><jtitle>Chirality (New York, N.Y.)</jtitle><addtitle>Chirality</addtitle><date>2013-11</date><risdate>2013</risdate><volume>25</volume><issue>11</issue><spage>763</spage><epage>767</epage><pages>763-767</pages><issn>0899-0042</issn><eissn>1520-636X</eissn><abstract>ABSTRACT
The occurrence of pharmaceuticals in the environment represents a challenge of emerging concern. Many pharmaceuticals are chiral compounds; however, few studies have examined the relative toxicity of pharmaceutical enantiomers to wildlife. Further, our understanding of stereospecific pharmacokinetics remains largely informed by research on humans and a few well‐studied laboratory test animals, and not by studies conducted with environmentally relevant species, including fish. The objective of this study was to investigate whether rainbow trout display stereospecific in vitro metabolism of three common chiral pharmaceuticals. Metabolism by trout liver S9 fractions was evaluated using a substrate depletion approach, which provides an estimate of intrinsic hepatic clearance (CLIN VITRO,INT). No biotransformation was observed for rac‐, R‐, or S‐fluoxetine. Ibuprofen, including both enantiomers and the racemic mixture, appeared to undergo slow metabolism, but the resulting substrate depletion curves did not differ significantly from those of inactive controls. Contrary to relative clearance rates in humans, S(−)‐propranolol was more rapidly cleared than the R(+)‐ enantiomer. This work demonstrates that relative clearance rates and the effects of racemic mixtures in trout could not have been predicted based on human data. Additional research describing species differences and exploring tools for species extrapolation in biomedical and environmental studies is needed. Chirality 25:763–767, 2013, © 2013 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>23893772</pmid><doi>10.1002/chir.22211</doi><tpages>5</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0899-0042 |
ispartof | Chirality (New York, N.Y.), 2013-11, Vol.25 (11), p.763-767 |
issn | 0899-0042 1520-636X |
language | eng |
recordid | cdi_proquest_miscellaneous_1758239307 |
source | Wiley |
subjects | Animals bioaccumulation Biotransformation Clearances comparative pharmacokinetics contaminants of emerging concern Depletion Enantiomers Environmental Pollutants - chemistry Environmental Pollutants - metabolism environmental risk assessment Human In vitro testing metabolic biotransformation Metabolism Oncorhynchus mykiss Oncorhynchus mykiss - metabolism Pharmaceutical Preparations - chemistry Pharmaceutical Preparations - metabolism Pharmaceuticals Stereoisomerism Substrate Specificity Trout |
title | Enantiomer-Specific In Vitro Biotransformation of Select Pharmaceuticals in Rainbow Trout (Oncorhynchus mykiss) |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T06%3A32%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Enantiomer-Specific%20In%20Vitro%20Biotransformation%20of%20Select%20Pharmaceuticals%20in%20Rainbow%20Trout%20(Oncorhynchus%20mykiss)&rft.jtitle=Chirality%20(New%20York,%20N.Y.)&rft.au=Connors,%20Kristin%20A.&rft.date=2013-11&rft.volume=25&rft.issue=11&rft.spage=763&rft.epage=767&rft.pages=763-767&rft.issn=0899-0042&rft.eissn=1520-636X&rft_id=info:doi/10.1002/chir.22211&rft_dat=%3Cproquest_cross%3E3107302441%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4611-a75734d094897d7c16cd3753960628a4e58ede82063b4bffea80b5a0b57df8433%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1444545657&rft_id=info:pmid/23893772&rfr_iscdi=true |